High risk Langerhans cell histiocytosis in children: the role of salvage in improving the outcome. A single center experience.

BACKGROUND: In pediatric multi-system high risk organs (RO +) Langerhans cell histiocytosis (LCH), failing 1st line treatment has the highest mortality. We aim to present the outcome of failure of 1st line whether due to disease progression (DP) at end of induction or reactivation (REA) after initial better status response. PATIENTS AND METHODS: Sixty-seven RO + LCH patients with hemopoietic, hepatic or splenic involvement, treated between 2007 and 2019 were retrospectively analyzed. The median follow-up (IQR) is 6 years (4-8.8 y).They were subjected to 2 eras of treatment; one with salvage by 2-Cda based regimen (2-CdABR) and another without. RESULTS: Of 67 patients, M/F 40/27, median age 1.74 y (0.2-10 y), 42 failed 1st line (62.7%). Of them DP n = 22 (52%) and REA n = 20 (48%). Of those with DP, 9/22 patients received 2-CdABR, where 5 survived in better status. While the remaining 13 did not receive 2-CdABR and all of them died. Otherwise, of those with REA, 12/20 reactivated on RO + mode. Of them, 8/12 received 2-CdABR, where only one survived in better status and the remaining 4 received vinblastine-based regimen,where 2 died and 2 were rescued. RO + 5-year overall survival (OS) was 65% (CI 95% 54 -78) while the event free survival (EFS) 36% (26.3-50.1). The OS of DP 27% (14-54) versus REA 67% (49-93) p 0.004. OS of DP with 2-CdABR 56% (31-97.7) versus 8% without (2-51), p < 0.001. While OS of REA with 2-CdABR 38% (13-100) versus 74% without (53-100) p 0.7. CONCLUSION: Survival of RO + remains limited. Failure of 1st line in RO + due to DP carries worse prognosis in relation to REA. In DP those who were not salvaged by 2-CdABR, showed dismal outcome. This could not be shown when applied in REA.

Skeletal involvement in children with Langerhans cell histiocytosis: healing, complications, and functional outcome.

INTRODUCTION: Skeletal involvement in children with Langerhans cell histiocytosis (LCH) is a common feature of the disease. Several options for the treatment of these skeletal lesions have been reported. We describe our experience in the treatment of skeletal involvement of LCH in this retrospective case series study, entailing anatomic distribution, pattern of healing, skeletal deformities, and functional outcome of skeletal LCH. METHODS: A retrospective analysis was conducted for patients diagnosed with LCH and having skeletal lesions in the period between 2007 and 2015. Out of a total of 229 cases, 191 (83.4%) had skeletal involvement. Bone healing was divided into partial and complete based on the size of lesion and cortical changes in plain radiograph. Skeletal deformities were serially measured. Time to pain control, resumption of weight bearing, and the final functional status of the patient were reviewed. RESULTS: The mean age at presentation was 4.4 years (3 m-14.8 y) and the mean follow-up period was 53.3 months (0.2-120.7). After screening of skeletal and extra-skeletal lesions, 59 patients (31%) had M-S (Multisystem) LCH and 132 (69%) had S-S (Single system) LCH. Unifocal bone lesions were found in 81 (42.5%) patients, and multifocal bone lesions in 110 patients (57.5%). Single or multiple bone lesions were found in the craniofacial bones in 152 patients (79.5%), femur in 19 patients, (10%), ribs in 18 patients (9.4%), spine in 15 patients (8.1%), pelvis in 14 patients (7.3%), scapula in 8 patients (4.1%), humerus in 6 (3.1%), clavicle in 6 patients (3.1%), tibia in 3 patients (1.5%), radius in 3 patients (1.5%), and the ulna in 2 patients (1%) patients. No lesions were found in the fibula, hand, or foot. Out of all skeletal lesions, 179 (93.7%) patients were treated either medically or conservatively and 12 patients (6.2%) were treated surgically. The mean time to complete healing was 5.2 months (2-12). Skeletal complications included: pathologic fractures (9 vertebra plana, 5 long bone, 1 iliac bone), deformities (9 thoracolumbar kyphosis, 2 cervical spine subluxations, 2 coxa vara deformity of the proximal femur and one flattening of iliac bone). CONCLUSION: Non-operative treatment can lead to adequate bone healing in few months period. Partial or complete remodeling of bone deformities can be observed without surgical correction. However, surgical intervention might be indicated when cervical spine affection may lead to instability and subsequent neurological affection. Functional impairment is rarely caused by skeletal lesions in LCH.

Outcomes of allogenic hematopoietic cell transplantation for childhood chronic myeloid leukemia: Single-center experience.

BACKGROUND/OBJECTIVES: Despite the apparent efficacy and favorable toxicity profile of TKIs, allogeneic SCT remains the only curative treatment for CML especially in younger patients, but TRM should be considered. We evaluated the clinical outcomes of pediatric CML patients who had SCT in our center. METHODS: This retrospective study included children with CML, who received an allogeneic SCT at Children Cancer Hospital Egypt, 57357, from 2007 to 2017. All patients received myeloablative conditioning chemotherapy containing busulfan/cyclophosphamide followed by stem cell infusion from MRD. RESULTS: From 121 patients diagnosed with CML, 43 had available MRD and subjected to HSCT while 78 patients continued TKI therapy. The median time to transplant from diagnosis was 13 months. At initial diagnosis, there were 39 patients in CP and 4 had blastic crises. Bone marrow harvest was the stem cell source in 32 patients, while 11 cases received mobilized peripheral blood stem cells with average stem cell dose of 4.45 × 106 /kg. The probabilities of overall survival and event-free survival at 5 years were 97.4% and 79.8%, respectively. TRM at 100 days and TRM at 1-year post-transplant were 0%. The incidence of chronic GVHD was significantly higher in peripheral blood than bone marrow stem cell source (P = .004). CONCLUSION: Considering the excellent survival rates and very low TRM, HSCT is still a valid option for pediatric patients with newly diagnosed CML with best using marrow stem cell source to avoid a significant risk of cGVHD and its related complications.

Overview and outcome of mucormycosis among children with cancer: Report from the Children's Cancer Hospital Egypt.

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Outcome of High-risk Langerhans Cell Histiocytosis (LCH) in Egyptian Children, Does Intermediate-dose Methotrexate Improve the Outcome?

High-risk multisystem organ (RO+) Langerhans cell histiocytosis (LCH) has the least survival. We present the outcome of RO+ LCH in a pediatric single center. Fifty RO+ LCH patients, treated between 07/2007 and 07/2015, were retrospectively analyzed. Induction vinblastine (VBL) and prednisone (PRED) with intermediate-dose methotrexate (idMTX) was adopted until 2012 (n=20) wherein idMTX was omitted (n=30). The 3-year overall survival (OS) of MTX and non-MTX groups was 75% and 63%, respectively, P=0.537, while the event-free survival (EFS) was 36.9% and 13.2%, respectively, P=0.005. At week 12 of induction, "better status" was obtained in 80% of those receiving MTX, and 55% of those who were not. The statistically significant factors associated with both poor OS and EFS were trihemopoietic cytopenias, hepatic dysfunction, tri RO+ combination, and single induction. The factors associated with disease progression (DP) on induction were trihemopoietic cytopenias, hepatic dysfunction, and lack of idMTX, while those for disease reactivations (REA), the season of autumn/winter, lung disease, male sex, and idMTX were the associated factors. The 1-year OS was remarkably affected with the occurrence of DP versus REA versus none, wherein it was 47%, 93%, and 95%, respectively, P=0.001. In conclusion, idMTX is associated with better EFS. DP on induction remains of dismal prognosis in relation to disease REA afterwards. Risk stratification should highlight the role of trihemopoietic cytopenias, hepatic dysfunction, tri RO+, central nervous system risk site, and lung association.